CCR5 governs DNA damage and breast cancer stem cell expansion

The functional significance of the chemokine receptor CCR5 in human breast cancer (BCa) epithelial cells is poorly understood. Here we report that CCR5 expression in human breast cancer correlates with poor outcome. CCR5+ BCa epithelial cells formed mammospheres and initiated tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5-negative BCa cells promoted tumor metastases and induced DNA repair gene expression and activity. CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing mediated by DNA-damaging chemotherapeutic agents. Single cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is re-expressed selectively on cancerous but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DDR-based treatments, allowing a dose reduction of standard chemotherapy and radiation.

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